Diazine derivatives



Patented Oct. 31', 1944 UNITED STATES PATENT OFFICE 2,361,822 nmznvn DERIVATIVES Gaetano F. DAlelio and James W. Underwood, Pittsfleld, Masa, assignora to General Electric Company, a corporation of New York No Drawing. Application May 21, 1942, Serial No. 443,979

20 Claims. ('01. 260-251) In the above formula n represents an integer and is at least 1 and not more than 2, x represents a halogen atom, more particularly a chlorine, bromine, fluorine or iodine atom, and R reprecents a member or the class consisting of hy drogen and monovalent hydrocarbon and substituted hydrocarbon radicals, more particularly halo-hydrocarbon radicals.

Illustrative examples of radicals that R in the above formulav may represent are: aliphatic (e. g., methyl, ethyl, propyl, isopropyl, butyl, secondary butyl, isobutyl, butenyl, amyl, isoamyl, hexyl, octyl, allyl, methallyl, ethallyl, crotyl, etc), including cycloaliphatic (e. g., cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, etc.) aryl (e. g., phenyl, diphenyl or xenyl, naphthyl, etc.); aliphatic-substituted aryl (e. g., tolyl, xylyl, ethylphenyl, propyl-phenyl, isopropylphenyl, allylphenyl, 2-butenylphenyl, tertiarybutyl-phenyl, etc); aryl-substltuted aliphatic (e. g., benzyl, phenylethyl, cinnamyl, phenylpropyl, etc); and their homologues, as well as those groups with one or more of their hydrogen atoms substituted by, for example, a halogen, more particularly chlorine, bromine, fluorine or iodine. Specific examples of halogeno-substituted hydrocarbon radicals ar chloromethyl, chloroethyl chlorophenyl, dlchlorophenyl, chlorocyclohexyl, ethyl chlorophenyl, phenyl chloroethyl, bromoethyl, bromopropyl, fluorophenyl, iodophenyl, bromotolyl, etc. Preferably R in the -NHR groupings of Formula I is hydrogen and the R in the COOR grouping is either hydrogen or an unsubstituted monovalent hydrocarbon radical, e. g., an aliphatic radical such as methyl,

ethyl, propyl, butyl, pentyl, hexyl, allyl, methallyl, crotyl, etc. However, there also may be produced in accordance with the present invention compounds such, for instance, as those represented by the general formulas:

1r (RHN)T- --sc.m.-.x -cooa] I \N/ J and, more particularly,

H N 11: (um),--- g (S --s[(c.H|..1c1)-coonq \N/ V and n-c \N I \N/ J where n, x and R have the same meanings as given above with respect to Formula I and R (Formulas III and IV) represents hydrogen or an unsubstituted monovalent hydrocarbon radical, numerous examples of which have been given above.

The new compounds of this invention may be used, for example, as pharmaceuticals, plasticizers and as intermediates in the preparation of derivatives thereof such as hydrazo, hydrazine, carbazido, semicarbazido, ureido, amidine, methylol, etc., derivatives of the individual compound embraced by Formula I. Compounds containing a -COOH grouping may be amidated: or the hydrogen of the carboxy grouping may be replaced by a substituent such, for instance, as an ammonium radical or a, monovalent metal, e. g., an alkali metal such as sodium, potassium, lithium, etc. Our new com-pounds are especially valuable in the preparation of synthetic resinous compositions. Thus, they may be condensed with, for instance, aldehydes, including polymeric aldehydes, hydroxyaldehydes and a1dehyde-addition products, to yield condensation products of particular utility in the plastics and coating arts. They are particularly useful as such or in the form of their soluble, iusible aldehyde-reaction products as agents for accelerating the conversion of acid-curing thermosetting resins, e. g., acid-curing thermosetting aminoplasts and phenoplasts, to an insoluble, infusible state. Aldehyde-reaction products of the diazine derivatives embraced by Formula I and acid-curing thermosetting resins containing the said diazine derivatives or their soluble, fusible aldehyde-reaction products'are more fully described and are specifically claimed in our copending application Serial No. 443,978, flied May 21, 1942. These new compounds also may be compounded with rubber. both natural and synthetic, to modify the properties of the rubber.

Various methods may be employed to produce the chemical compounds 01 this invention. We prefer to prepare them by efiecting reaction, in the presence of a hydrohalide acceptor, between equimolecular proportions of a mercapto (monomercapto) diamino p:*rimidine and a carboxy-, carboaliphaticoxy= or carboaromaticoxy-alkyl dihalide. When a carboxy (-COOH) alkyl dihalide is used as a starting reactant and the proportions of reactants and reaction conditions are such that the hydrogen atom of the --COOH grouping is replaced by the residue of the hydrohalide acceptor, e. g., by an alkali metal, the carboxy compound desired as a final product is obtained by treating this intermediate product with hydrochloric, hydrobromic, sulfuric or other suitable inorganic or organic acid in an amount just suflicient to form the desired carboxy derivative.

Illustrative examples of diamino mercapto pyrimidines that may be employed, depending upon the particular end-product sought, are:

6-isopropyla- Z-mercapto 4,6-di-(methylamino) pyrimidine 2-mercapto 4,6-di-(iluorophenylamino) pyrimidine 4-mercapto 2,6-di-(methylamino) pyrimidine 2-mercapto 4,6-di-(methylamino) 5-methyl pyrimidine 4-mercapto 2,6-di-(methylamino) 5-phenyl pyrimidine -2-mercapto 4-chloroethylarnino 6-methylamino pyrimidine 2-mercapto 4,6-di-(anilino) pyrimidine 2-mercapto 4,6-di-(anilino) S-butyl pyrimidine 2-mercapto 4-xenylamino 5-cyclopentyl 6-amylamino pyrimidine 2-toluido 4-mercapto 5-cyclohexenyl 6-amino pyrimidine (2-to1uido 4-amino 5-cyc1ohexenyl G-mercapto pyrimidine) 2-mercapto 4-amino fi-ethylamino pyrimidine 2-mercapto 4,6-di-(propylamino) pyrimidine 2-a1lylamino 4-mercapto 6-chlorophenylamin0 pyrimidine Z-amylamino i-mercapto 5-phenyl d-amino pyrimidine 2-dichloroanilino i-mercapto 5-tolyl G-propylamino pyrimidine z-eycloheptylamino 4-mercapto S-isobutylamino pyrimidine 2-mercapto 4-allylamino fi-butylamino pyrimidine 2-mercapto 4-(3'-butenylamino) amino pyrimidine Z-mercapto i-isobutylamino G-cyclopentylamino pyrimidine Z-mercapto 4-isobutyiamino 5-propyl 6-cyclopentylamino pyrimidine Z-mercapto 4-amino d-chloroxenylamino pyrimidine I Z-mercapto i-ethylphenylamino B-naphthyl 6- xylidino pyrimidine Z-mercapto 4-phenethylamino 5-(2'-butenyl) 8- cyclopentenylamino pyrimidine 2-g1iemapto 4,6-diamino 5-bromotolyl pyrimi- Z-mercapto i-amino 5-phenylisopropyl 6-chlorocyclohexylamino pyrimidine Z-mercapto 4-isobutylamino B-bromonaphthylamino pyrimidine Z-ggercapto 4,6-di-(iodophenylamino) pyrimi- Illustrative examples of carboxy-, carboaliphaticoxyand carboaromaticoxy-alkyl dihalides that may be used, depending upon the desired end-product, are:

Dichloro carboxy methane Dibromo carboxy methane The dichloro carboalkoxy (e. g., carbomethoxy. carboethoxy, carbopropoxy, carbobutox etc.) methanes The dibromo carboalkoxy methanes The dichloro carboaroxy (e. g., carbophenoxy.

carbonaphthoxy, etc.) methanes The dibromo carboaroxy methanes The dichloro carboalkoxy ethanes The dibromo carboalkoxy ethanes The diiodo carboalkoxy ethanes The dichloro carboaroxy ethanes The dibromo carboaroxy ethanes The diiodo carboaroxy ethanes Alpha,beta-dichloro carboethoxy ethane Alpha,beta-bibromo carboethoxy ethane Alpha,alpha-dichloro carbobutoxy ethane Alpha,alpha-dibromo carbobutoxy ethane Alpha,alpha-dichloro carboethoxy ethane Alpha,alpha-dibromo carboethoxy ethane Beta,beta-dichloro carboethoxy ethane Beta,beta-dibromo carboethoxy ethane Beta;beta-dichloro carbopropoxy ethane Beta,beta-dibrom carbopropoxy ethane 6-isopropyl- Alphaaipha-dichloro carbopropoxy ethane Alpha,alpha-dibromo carbopropoxy ethane Alpha,beta-dichloro carbopropoxy ethane Alpha,beta-dibromo carbopropoxy ethane Alpha,alpha-diiodo carboethoxy ethane Alpha,alpha-diiodo carbophenoxy propane Alpha-bromo alpha-iodo gamma-phenyl carbonaphthoxy propane Beta,beta-dichloro carbotoloxy ethane Beta-isobutyl beta,beta-dibromo carbo-xyloxy ethane Alpha-chlorophenyl beta-naphthyl beta,betadiido carbobenzoxy ethane Alpha-cyclopentyl alpha-tolyl beta-chloro betaiodo carbophenethoxy propane Alpha-benzyl beta cyclohexyl alphabeta dichloro carbocyclopentoxy pentane Alpha-xylyl beta,beta-diphenyl alpha,beta-dibromo carbocyclohexoxy ethane Alpha-bromonaphthyl alpha,beta-dichloro carbophenoxy ethane Beta-phenyl alpha,beta-dichloro carboethoxy propane Beta-ethyl alpha,beta-dibromo carbophenoxy Various hydrohalide acceptors may be em-' ployed. We prefer to use a may be carried out under a variety of temperature and pressure conditions, for instance at normal, sub-normal or at elevated temperatures and at atmospheric, sub-atmospheric 0r super-atmospheric pressures.

The above reaction may be represented by the beta-cresyl beta-tolyl be carried into elect. the to Ilium-cu examples are given. All parts are by weight.

diamino pyrimidyl-2 bromo carbomethoxy-ethyl sulfide, the formula for which is where n has a value of 2.

2-mercapto 4,6-diamino pyrimidine Alphabetsdibromo carbomethoxy ethane Sodium hydroxide 20.0

I Water 1250.0

where stirred together rapidly at room temperature for 3 hours, yielding a precipitate comprising 4,6-diamino pyrimidyl-2 bromo carbome E's-ample 2 2,6-diamino pyrimidyl-4 bromo carbomethoxyethyl sulfide is prepared in essentially manner as described under Example 1 with the exception that Q-mercapto 2,6-diamino pyrimidine ls'used instead or Z-mercapto 4,6-diamino 35 pyrimidine.

following general equation: alpha.beta-dichloro carbomethoxy ethane is used.

1 hyaromiiidc R-o N (RHNII g --SH+(C.R1--1Xr)-COOR if? \K J v a-c \N I salt of v mm g s-[ c.a....x)-coom+hy m um .1 p men In the above equation n, R and X have the 55 Example 4 same meanings as given above with reference to Fbrmula. I.

preparation.

In order that those skilled in the art better may understand how the present invention may 4,6-di-(methylamlno) pyrlmidyi-2 hm carbomethoxy-ethyl sulfide is prepared in essentially under Example 1' with the exception that, instead 01' 2-mercapto the same manner as described 4,6-diamino pyrimidine, an equivalent amount of Z-mercapto 4,6-di-(methylamino) pyrimidine is.

used. I

Examples 4,6-diamlno pyrimidyl-2 ethyl sulfide is prepared in manner as described under Example 6 exception that, instead of alpha,beta-dibromo carbomethoxy ethane, an equivalent amount of alpha,beta-dlch10ro carbopherioxy ethane is used.

Other examples of the chemical compounds of this invention are listed below:

l The diamino pyrimidyl halogeno carboaliphatlcoxy-methyl sulfides, including the diamino pyrimidyl chloro carboaliphaticoxy-methyl sulfides, the diamino pyrimidyl bromo carboaliphaticoxy-methyl sulfides, the diamino pyrimidyl iodo carboaliphaticoxy-methyl sulfides and the diamino pyrimidyl fiuoro carboaliphaticoxymethyl sulfides, more particularly the diamino pyrimidyl halogeno (e. g., chloro, 'bromo, etc.) aikoxy (e. g., methoxy, ethoxy, propoxy, butoxy, etc.) -methyl sulfides The diamino pyrimidyl halogeno carboaroxymethyl sulfides, more particularly .the diamino pyrimidyl chloro carboaroxy-methyl sulfides, the diamino pyrimidyl bromo carboaroxymethyl sulfides, the diamino pyrlmidyl iodo carboaroxy-methyl sulfides and the diamino Dyrimidyl fiuoro carboaroxy-methyl sulfides The diamino pyrimidyl halogeno (chloro, bromo,

iodo, fiuoro) carboxy-methyl sulfides The diamino pyrimidyl halogeno (chloro, bromo,

iodo, fiuoro) carbcaliphaticoxy (e. g., carboalkoxy) -ethyl sulfides The diamino pyrimidyl halogeno (chloro, bromo, iodo, fiuoro) carboaroxy (e. g., carbophenoxy, carbotoloxy, etc.) -ethyl sulfides 2,6-diamino pyrimidyl-4 chloro carbomethoxyethyl sulfides 2,6-di-(methylamino) pyrimidyl-4 bromo carbomethoxy-ethyl sulfides 2,6-diamino pyrimidyl-4 bromo carbophenoxyethyl sulfides 4,6-diamino pyrimidyl-2 chloro carbophenoxyethyl sulfides 2,6-diamino pyrimidyl-4 chloro carbophenoxyethyl sulfides 4-amino G-methylamino pyrimidyl-Z bromo carboxy-methyl sulfide 4,6-diamino -methyl pyrimidyl-2 chloro carbomethoxy-methyl sulfide 4-pentylamino fi-benzylamino 5-naphthyl pyrimidyl-2 alpha-(beta-iodo carbomethoxy-ethyl) sulfide 2,6-di-(anilino) 5-benzyl pyrimidyl-4 beta-(alpha-bromo carbophenoxy) sulfide 2,6-di-(benzylamino) 5-cyclopentyl pyrimidyl-4 alpha-(alpha-chloro carbotoloxy-ethyl) sulfide 2-toluldo 6-xylidlno 5-tolyl pyrimidyl-4 beta- (beta-iodo carbobenzoxy-pentyl) sulfide 4,6-di-(ethylamino) pyrlmidyl-2 chloro carboxymethyl sulfide 4,6-di-(anilino) pyrimidyl-Z chloro methyl sulfide 4,6-di-(bromoanilino) pyrimidyl-2 bromo carboxy-methyl sulfide 4,6-di-(cyclohexylamino) pyrimldyl-2 chloro carboxy-methyl sulfide 4,6-diamino pyrimiclyl-2 alpha-(alpha-chloro carbomethoxy-methyl) sulfide 2,6-diamino 5-methyl pyrimidyl-4 beta-(betabromo carboethoxy-ethyl) sulfide 4,6-diamino 5-phenyl pyrimidyl-Z alpha-(betachloro carbopropoxy-ethyl) sulfide 2,6-diamino pyrimidyl-4 beta-(alpha-chloro carboethoxy-ethyl) sulfide 4,6-di-(methylamino) pyrimidyl-2 bromo carbobutoxy-methyl sulfide carboxy- 4,6-diamino pyrimidyl-Z alpha-(alpha-chloro carbophenoxy-ethyl) sulfide 4,6-diamino pyrimidyl-2 beta-(beta-bromo carbophenoxy-ethyl) sulfide 5 2,6-d1amino 5-propyl pyrimidyl-4 alpha-(betachloro carbophenoxy-ethyl) sulfide 2,6-diamino 5-chlorophenyl pyrimidyl-4 beta- (alpha-bromo carbophenoxy-ethyl) sulfide 4,8-diamlno pyrimidyl-2 alpha- (alpha-chloro carbophenoxy-propyl) sulfide 4,6-di-(anilino) pyrimldyl-Z alpha-(alpha-iodo carbophenoxy-propyl) sulfide 4,6-di-(cyclopentylamino) 5-chloroethyl pyrimidyl-2 alpha-(gamma-phenyl alpha-chloro carbonaphthoxy-propyl) sulfide d-ethylamino S-methyl 6-amino pyrimidy1-2 beta- (beta-chloro carbotoloxy-ethyl) sulfide 4-isobutylamino S-neopentylamino pyrimidyl-Z beta-(alpha-phenyl beta-naphthyl beta-iodo carbobenzoxy-ethyl) sulfide Z-naphthylamino fi-fiuorophenyl 6-amino pyrimidyl-4 beta-(beta-isobutyl beta-bromo carboxyloxy-ethyl) sulfide 4-benzylamino fi-toluido pyrimidyI-Z beta- (alphatolyl alpha-cyclopentyl beta-chloro carbophenethoxy-propyl) sulfide 4-phenethylamino 6-xylldino pyrimidyl-2 alpha- (alpha-phenethyl beta-phenyl beta-bromo carbocyclopentoxy-ethyl) sulfide 4,6-dlamino pyrimldyl-2 alpha- (alpha-chloro carboxy-ethyl) sulfide 2,6-diamino pyrimldyl-4 beta-(beta-bromo carboxy-ethyl) sulfide 4,8-diamino 5-iodophenyl pyrimidyl-2 alpha- (beta-iodo carboxy-ethyl) sulfide 4,6-diamino pyrimidyl-2 beta-(alpha-bromo carboxy-ethyl) sulfide 4-cyclopentenylamino B-chloroxylidino pyrimidyl- 2 beta-(alpha-chloro beta-benzyl carboethoxypropyl) sulfide e-amino G-methylamino pyrlmidyl-2 alpha-(betachlorophenyl beta-chloro carboethoxy-ethyl) sulfide It will be understood, of course, by those skilled in the art that, in those compounds listed above that are generically named, the amino (--NHR) groups and the thio group may be attached in any arrangement to the symmetrical carbon atoms of the pyrimidine nucleus. In other words, the term "diamlno pyrimidyl includes within its meaning both the 4,6-diamino pyrimidyl-2 and the 2,6-diamino pyrlmidyl-4 (2,4-diamino pyrimidyl-6) compounds.

In a manne similar to that described above with particular reference to the diamino [(NHR)2] pyrimidyl halogeno carboxy-, carboaliphaticoxyand carboaromaticoxy-methyl and -ethyl sulfides, corresponding derivatives of the 1,2- or ortho-diazines (pyridazlnes) and oi the 1,4- or para-diazines (pyrazines) may be prepared. It also will be understood by those skilled in the art from the foregoing descriptionof the preparation of a diazine monosulfide that similar compounds may be prepared in which two or three sulfur atoms are attached directly to a carbon atom of the diazine nucleus and which have attached to each sulfur atom a grouping, where n, X and B have the same meanings as given above with reference to Formula I. What we claim as new and desire to secure by 75 Letters Patent of the United States is:

1. Chemical compounds corresponding to the general formula where n represents an integer and is at least 1 and not more than 2, X represents a halogen atom, and R represents a member of the class consisting of hydrogen and monovalent hydrocarbon and halo-hydrocarbon radicals.

2. Chemical compounds as in claim 1 wherein R represents a hydrogen atom.

3. Chemical compounds as in claim 1 wherein x represents a chlorine atom.

4. Chemical compounds as in claim l-wherein x represents a bromine atom.

5. Chemical compounds corresponding to the general formula where n represents an integer and is at least 1 and not more than 2. X represents a halogen atom, and R represents a member of the, class consisting of hydrogen and monovalent hydrocarbon and halo-hydrocarbon radicals.

6. Chemical compounds corresponding to the general formula where n represents an integer and is at least 1 and not more than 2, and R represents a member of the class consisting of hydrogen and unsubstituted monovalent hydrocarbon radicals.

'7. Chemical compounds corresponding to the general formula where n represents an integer and is at least. 1 and not more than 2, and R ber of the class consisting of hydrogen and unsubstituted monovalent hydrocarbon radicals.

8. A diamino pyrimidyl haiogeno 'carboaliphaticoxy-ethyl sulfide.

9. A diamino pyrimidyl chloro carboalkoxyethyl sulfide.

10. A 4,6-diamino pyrimidyl-2 chloro carbomethow-ethyl sulfide.

represents a mom-- 11. A diamino pyrimidyl bromo carboaikoxyethyl sulfide.

12. A 4,6-diamino pyrimidyl-2 bromo carbomethoxy-ethyl sulfide.

13. A diamino pyrimidyl halogeno carboaromaticoigv-ethyl sulfide.

14. A diamino pyrimidyi chloro carboaromaticoxy-ethyl sulfide.

15. A 4,6-diamino pyrimidyl-2 chloro carbophenoxy-ethyl sulfide.

16. The method of preparing chemical compounds corresponding to the general formula where n represents an integer and is at least 1 and not more than 2, x represents a halogen atom. and R. represents a member of the class consisting of hydrogen and monovalent hydrocarbon and halo-hydrocarbon radicals, said method comprising effecting reaction, in the presence of a hydrohallde acceptor, between approximately equimolecular proportions of (1) a mercapto pyrimidine corresponding to the general formula (nim j ii-4am V where R has the meaning above given, and (2) a compound corresponding to the general formula (c-nanxn -CO0R.

where n, x and R have the meanings above given.

17. A method as in claim 16 where X represents a chlorine atom and the hydrohalide acceptor is an alkali-metal hydroxide.

thoxy ethane.

GAE'I'ANO I". D'ALELIO. JAMES W. UNDERWOOD. 

